利拉鲁肽对急性心肌梗死大鼠心肌纤维化影响的实验研究

Experimental Study of Inhibited Myocardial Fibrosis by Liraglutide Following Acute Myocardial Infarction in Rats

目的:观察利拉鲁肽对急性心肌梗死大鼠心肌纤维化的影响并探讨其可能的机制。方法:结扎左冠状动脉前降支制作急性心肌梗死大鼠模型,随机分为对照组(6只),利拉鲁肽低剂量组(LS组,0.09mg·kg-1·d-1)和利拉鲁肽高剂量组(HS组,0.18·kg-1·d-1),另设假手术组(6只),建模4周后,超声心动图评估大鼠心脏结构及功能,心肌Sirius-red染色法测定心肌胶原密度,TUNEL法检测心肌细胞凋亡水平,Western blot法检测心肌Pro caspase3、cleaved caspase3、PARP、TGF-β1和MMP-9表达。结果:与假手术组相比,对照组LVEF、LVFS降低,LVEDd、LVESd升高,差异有统计学意义(P<0.05);LS组和HS组LVEF、LVFS高于对照组,而LVEDd和LVESd较对照组有所下降(P<0.05),且HS组较LS组改善更明显,差异均有统计学意义(P<0.05);Sirius-red染色结果示LS组和HS组胶原纤维含量均低于对照组,差异有统计学意义(P<0.05),而LS组和HS组间无明显差异;TUNEL染色结果显示LS组和HS组凋亡细胞较对照组明显减少(P<0.05);Western blot结果提示LS组和HS组心肌组织TGF-β1、MMP-9、caspase-3和PARP蛋白表达量均低于对照组,差异有统计学意义(P<0.05),HS组心肌组织TGF-β1、MMP-9、caspase-3和PARP蛋白表达量有低于LS组的趋势,但差异无统计学意义(P>0.05)。结论:利拉鲁肽可减轻大鼠急性心肌梗死后心肌纤维化,其机制可能抑制TGF-β1和MMP-9表达及抗心肌细胞凋亡相关。

Objective:To investigate the effects of Liraglutide on myocardial fibrosis in rats after acute myocardial infarction(AMI).Methods:The rat model of AMI was established by occlusion of the left anterior descending artery.The AMI rats were randomly divided into 3 groups:Control group(n=6),Low dose liraglutide(LS)group(n=6,0.09mg·kg-1·d-1)and high dose liraglutide(HS)group(n=6,0.18mg·kg-1·d-1).Sham operation group(n=6),rats received normal saline.4 weeks later,cardiac structure and function were assessed by echocardiography;collagen volume fraction was calculated by Sirius-redstaining;the apoptotic myocardial cells were detected by TUNEL method;Pro caspase3,cleaved caspase3,PARP,TGF-βand MMP-9 were determined by Western blotting.Results:Compared with Sham operation group,control group showed decreased LVEF,LVFS and increased LVEDd,LVESd(P<0.05).Compared with control group,LS group and HS group had obviously increased LVEF,LVFS and decreased LVEDd,LVESd(P<0.05).Collagen volume fraction and apoptotic index were significantly decreased in LS group and HS group when compared with control group(P<0.05).The expression of Pro caspase3,cleaved caspase3,PARP,TGF-βand MMP-9 were significantly decreased in LS group and HS group in compared with control group(P<0.05).Conclusion:Liraglutide can reduce myocardial fibrosis in rats after AMI which partly contributes to attenuate the expression of TGF-βand MMP-9 and reduce myocardial cell apoptosis.